Department of Human Cell Biology and Genetics, School of Medicine, Southern University of Science and Technology, 1088 Xueyuan Avenue, Shenzhen, 518055, P.R. China.
Basic Science Institute, Sungkyunkwan University, Suwon, South Korea.
Cell Commun Signal. 2023 Nov 16;21(1):327. doi: 10.1186/s12964-023-01267-1.
Regulated cell death (RCD) is a regulable cell death that involves well-organized signaling cascades and molecular mechanisms. RCD is implicated in fundamental processes such as organ production and tissue remodeling, removing superfluous structures or cells, and regulating cell numbers. Previous studies have not been able to reveal the complete mechanisms, and novel methods of RCD are constantly being proposed. Two metal ions, iron (Fe) and copper (Cu) are essential factors leading to RCDs that not only induce ferroptosis and cuproptosis, respectively but also lead to cell impairment and eventually diverse cell death. This review summarizes the direct and indirect mechanisms by which Fe and Cu impede cell growth and the various forms of RCD mediated by these two metals. Moreover, we aimed to delineate the interrelationships between these RCDs with the distinct pathways of ferroptosis and cuproptosis, shedding light on the complex and intricate mechanisms that govern cellular survival and death. Finally, the prospects outlined in this review suggest a novel approach for investigating cell death, which may involve integrating current therapeutic strategies and offer a promising solution to overcome drug resistance in certain diseases. Video Abstract.
程序性细胞死亡（RCD）是一种可调控的细胞死亡，涉及到组织有序的信号级联和分子机制。RCD 参与了器官发生和组织重塑等基本过程，可清除多余的结构或细胞，并调节细胞数量。先前的研究未能揭示完整的机制，新的 RCD 方法也在不断提出。两种金属离子，铁（Fe）和铜（Cu），是导致 RCD 的重要因素，它们不仅分别诱导铁死亡和铜死亡，还导致细胞损伤，最终导致多种细胞死亡。本综述总结了 Fe 和 Cu 抑制细胞生长的直接和间接机制，以及这两种金属介导的各种 RCD 形式。此外，我们旨在阐明这些 RCD 与铁死亡和铜死亡的不同途径之间的相互关系，揭示了控制细胞存活和死亡的复杂而精细的机制。最后，本综述中提出的前景表明了一种研究细胞死亡的新方法，该方法可能涉及整合当前的治疗策略，并为克服某些疾病中的药物耐药性提供有希望的解决方案。
